Friedman et al. (1), in this issue of the Journal, compared the outcome of Medicare patients age >65 years with heart failure (HF), an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, and an apparent indication for cardiac resynchronization therapy (CRT), who received either an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization therapy-defibrillator (CRT-D) device as a first elective implant. Of the 10,946 eligible patients included between 2006 and 2009 in the U.S. National Cardiovascular Data Registry (NCDR), 9,525 (87%) received CRT-D, showing a rapid uptake of evidence by implanters (2). QRS duration and morphology and the expertise of the implanter, but not the severity of renal dysfunction, influenced device choice. Current guidelines recommend that patients with heart failure and a left ventricular ejection fraction persistently <35% despite an adequate trial of pharmacological therapy, who are expected to survive with a reasonable quality of life for ≥1 year should receive an ICD, and if QRS duration is prolonged, this should often be CRT-D (3,4). Guidelines caution against implanting devices into patients with recently decompensated HF (44% of implants in NCDR were nonelective) but make no specific recommendation to avoid patients with renal dysfunction.

This analysis provides little idea on what the appropriate rate of device implantations should be. Accurate estimation is confounded by the surprising deficiency of robust data on the contemporary epidemiology of HF; possibly the world’s most common malignant condition (5,6). There are about 40 million people age >65 years in U.S. Medicare, so the implantation rate for this analysis was an average of just 68 patients per million per year (pmpy). Another analysis of the same dataset that did not exclude patients with renal dysfunction reported that 96,380 patients had received CRT-D during this period (7), or about 24,000 per year or 600 pmpy, which is similar to the contemporaneous age-adjusted rate for CRT/CRT-D in the United Kingdom (8). In the overall U.S. population age >65 years, new implants of CRT-D/ICD may now be about 1,000 pmpy, with more than one-half of these being CRT-D devices (9). These rates should be placed in the context of an estimated incidence of HF in the United States among people age >65 years of >6,000 pmpy and prevalence >75,000 per million, with perhaps one-third of these having a left ventricular ejection fraction <35% (6). Thus, in the United States, only a minority of likely eligible patients appear to receive a device.

In the current analysis, patients who received CRT-D rather than an ICD had a modest (15% to 20%) reduction in the risk of hospitalization for HF and death, consistent with a recent individual patient-data meta-analysis of randomized trials (10). Although no statistically significant interaction was observed with renal function, no benefit to implanting a CRT-D device was observed in those with an eGFR <15 ml/min/1.73 m2; data for dialysis patients were not published. Most patients with HF age >65 years have an eGFR <60 ml/min/1.73 m2(11), including those in the landmark trials that failed to identify an interaction between renal function and the effects of CRT. Therefore, this analysis supports, but does not greatly extend, existing information. However, because renal dysfunction is associated with a high mortality, CRT is likely to prevent more deaths in absolute terms among those with moderate renal dysfunction.

A major limitation of the current analysis is the lack of a device-free control group. Patients with a low eGFR or moderate-to-severe symptoms of HF may not benefit from an ICD (12,13). ICDs save, monotonously, 1 or 2 lives per year for every 100 devices implanted (14). On average, patients have to avoid dying of other things for quite some time to benefit from an ICD. ICDs are probably not cost-effective in less than a 5-year timeframe (15), which guidelines should reflect. The failure to follow guidelines on ICDs in the United States may largely reflect sensible clinical practice.

Over 3 years, the incidence of end-stage renal disease was <8%, and this was not substantially lower in those who received CRT. However, delaying death will have exposed patients to greater risk. The causes of renal dysfunction in HF are complex, reflecting pre-existing renal damage, pharmacological treatment, and net renal perfusion pressure (16). CRT can do nothing to improve the first 2, but increases in arterial and falls in venous pressure might improve renal perfusion and delay or reverse renal dysfunction (Online Table)(2,17). The renal response to CRT is likely to be heterogeneous and may be a further reason why it has been so difficult to predict its effect (18).

Were the criteria for CRT eligibility in this report appropriate? This should be judged both from the perspective of contemporary and of future guidelines (3,4). Almost one-half of the patients who received an ICD had a QRS duration >150 ms, but there may have been good reasons for this choice, such as unsuitable venous anatomy. Patients with QRS morphology other than left bundle branch block were less likely to get CRT-D in accordance with contemporary guidelines, but because this recommendation is no longer supported by the evidence, it may change (19). Better outcome with CRT-D for patients with left bundle branch block may reflect the fact that these patients have longer QRS duration and are less likely to have ischemic heart disease. Almost a quarter of those who received CRT-D had a QRS duration <140 ms. The next iteration of the guidelines is likely to recommend that QRS duration should exceed 130 or even 140 ms before considering CRT (19,20). More than one-third of patients had atrial fibrillation, for which there is little evidence of benefit from CRT (21). These issues require continual scrutiny to ensure appropriate guideline recommendations and device use.

Hopefully, clinicians do not mindlessly apply guidelines but offer treatments for a purpose useful to the patient. Within 3 years, 61% of those with end-stage renal disease who received an ICD and 54% of those who received CRT-D had died. Presumably, mortality would be even higher in those patients who were also age >75 years, the average age of patients in this analysis. Implanting a CRT pacemaker can be justified to improve symptoms, even if prognosis is grave. However, ICDs are ineffective and inappropriate for most patients with advanced disease. Opinion polls on both sides of the North Atlantic show that the great majority of the population believe that patients have the right to choose to die (22). In some Western European countries, up to 1 in every 20 deaths is now physician-assisted at the patient’s request (22). Rather than implanting, at some risk and discomfort, an expensive piece of technology, which may be attended by substantial morbidity, that may prolong death rather than prolong life, is it not better to have a frank discussion with the patient about the limits of modern medicine?

Appendix

Appendix

For a supplemental table, please see the online version of this article.

Footnotes

↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

Dr. Cleland has received research grants from Amgen, Novartis, Philips, and Servier; has served on advisory boards and speakers bureaus for Abbot, Amgen, Bayer, Medtronic, Philips, Servier, Stealth Biopharmaceuticals, and Vifor; and has served on the data and safety monitoring boards for Medtronic, Sorin, and Trevena. Dr. Mareev has received educational support from Sorin, Medtronic, and Boston Scientific.

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